دورية أكاديمية

Ubiquitin Ser65 phosphorylation affects ubiquitin structure, chain assembly and hydrolysis.

التفاصيل البيبلوغرافية
العنوان: Ubiquitin Ser65 phosphorylation affects ubiquitin structure, chain assembly and hydrolysis.
المؤلفون: Wauer, Tobias, Swatek, Kirby N, Wagstaff, Jane L, Gladkova, Christina, Pruneda, Jonathan N, Michel, Martin A, Gersch, Malte, Johnson, Christopher M, Freund, Stefan MV, Komander, David
المصدر: EMBO Journal; Feb2015, Vol. 34 Issue 3, p307-325, 19p
مصطلحات موضوعية: UBIQUITIN, PHOSPHORYLATION, HYDROLYSIS, CRYSTAL structure, C-terminal binding proteins
مستخلص: The protein kinase PINK1 was recently shown to phosphorylate ubiquitin (Ub) on Ser65, and phosphoUb activates the E3 ligase Parkin allosterically. Here, we show that PINK1 can phosphorylate every Ub in Ub chains. Moreover, Ser65 phosphorylation alters Ub structure, generating two conformations in solution. A crystal structure of the major conformation resembles Ub but has altered surface properties. NMR reveals a second phosphoUb conformation in which β5-strand slippage retracts the C-terminal tail by two residues into the Ub core. We further show that phosphoUb has no effect on E1-mediated E2 charging but can affect discharging of E2 enzymes to form polyUb chains. Notably, UBE2R1- ( CDC34), UBE2N/ UBE2V1- ( UBC13/ UEV1A), TRAF6- and HOIP-mediated chain assembly is inhibited by phosphoUb. While Lys63-linked poly-phosphoUb is recognized by the TAB2 NZF Ub binding domain ( UBD), 10 out of 12 deubiquitinases ( DUBs), including USP8, USP15 and USP30, are impaired in hydrolyzing phosphoUb chains. Hence, Ub phosphorylation has repercussions for ubiquitination and deubiquitination cascades beyond Parkin activation and may provide an independent layer of regulation in the Ub system. [ABSTRACT FROM AUTHOR]
Copyright of EMBO Journal is the property of Wiley-Blackwell and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)
قاعدة البيانات: Complementary Index
الوصف
تدمد:02614189
DOI:10.15252/embj.201489847